The mast cell precursor in human peripheral blood is CD34+/Fc(epsilon)RI-, gives rise to mast cells in the presence of recombinant human stem cell factor (SCF) with or without IL-3, and the number of mast cells arising per CD34+ cell in culture is greater when the CD34+ cells are obtained from patients with mastocytosis compared to normal subjects. The degree of abnormality on initial bone scan and progression of scintigraphic abnormalities with serial scanning in patients with mastocytosis correlate with the presence of more aggressive systemic mastocytosis. In many cases this may be a reflection of bone marrow expansion, which in turn probably reflects increased marrow disease. An analysis of cytokine profiles in dermal suction blisters has demonstrated that mastocytosis patients over-produce TNF-alpha. Mast cell tryptase in patients with mastocytosis differs from tryptase released during anaphylaxis. This difference is recognized by specific monoclonal antibodies and may allow the development of a more specific diagnostic test for mastocytosis. Studies are underway to examine c-kit for point mutations that may relate to the etiology of mastocytosis.